<i>PCDHGB7</i> : A universal cancer-only marker (UCOM) and novel diagnostic tool for diverse tumors.

Abstract

e15068 Background: The heterogeneity of tumors promoting the development of precision medicine，however, tumors also share certain common Hallmarks, suggesting the existence of common epigenetic mechanisms. Aberrant DNA methylation is consistently present throughout the process of tumor formation, especially in the pre-cancerous stage, and identification of common biomarkers in tumors is urgently needed. we have successfully developed Guide Positioning Sequencing (GPS) to cover more than 96% CpG sites. By the GPS, we have identified a group of methylation sites that are observed in more than 17 cancer types, termed as Universal Cancer-Only Marker (UCOM), which holds potential for broad application across diverse cancer types. While hrHPV screening has reduced cervical cancer incidence, an effective triage strategy for hrHPV-positive women is still needed to minimize unnecessary colposcopy referrals. Similarly, current urothelial carcinoma (UC) detection methods are invasive and lack sufficient sensitivity and specificity. Therefore, more accurate and practical diagnostic tools for multiple cancer types are required. PCDHGB7 , a UCOM, shows promise as a noninvasive marker for detecting hypermethylated PCDHGB7 in cervical and UC. Methods: In the cervical cancer cohort, 3251 Thinprep Cytologic Test (TCT) samples from hrHPV positive women will be collected and divided into training and validation group to evaluate the performance of PCDHGB7 in detecting cervical cancer (ChiCTR2100048972). In the UC cohort, PCDHGB7 hypermethylation in urine samples from urothelial carcinoma (UC) patients, to explore its utility in noninvasive UC detection (ChiCTR2100052507). Results: For cervical cancer, PCDHGB7 detection demonstrated high sensitivity (82.4%) and specificity (91.1%) in distinguishing cervical intraepithelial neoplasia grade 2 (CIN2) or worse from normal cases. It showed superior specificity (92.1% vs. 74.9%) and sensitivity (80.8% vs. 61.5%) compared to cytology, particularly among women positive for HPV16/18 and other hrHPV types. In the UC cohort, PCDHGB7 hypermethylation exhibited exceptional sensitivity (87.3%) and specificity (91.0%) in distinguishing UC from BUD patients. It outperformed standard urine cytology in detecting bladder cancer (82.1% vs. 34.5%), ureter cancer (78.1% vs. 34.4%), and renal pelvis cancer (90.9% vs. 22.7%). Conclusions: The detection of PCDHGB7 hypermethylation holds significant promise as a UCOM for diagnosing diverse cancers. In cervical cancer, it offers a noninvasive, highly accurate triage strategy for hrHPV-positive women, reducing unnecessary colposcopy referrals. In UC, PCDHGB7 detection provides an effective, noninvasive method for early diagnosis. Overall, PCDHGB7 has the potential to revolutionize cancer diagnostics by offering a versatile, high-performance tool for multiple tumor types. Clinical trial information: ChiCTR2100052507 .